The ability to rapidly distinguish superfamilies of proteins which have a conserved structural fold and perform a fundamentally similar chemistry has become increasingly important. It provides a method of predicing the function of unknown proteins, and can be used to value a protein's potential as a drug target. We have designed the Shotgun program to identify the members of protein superfamilies using sequence information alone. The methodology behind Shotgun is simple enough to not be a "black box" to biological researchers, and our control experiments show that the method is fundamentally sound. We have used Shotgun to reconstruct superfamilies whose relationships were discovered through structure versus structure comparisons, and to find new members of several superfamilies. The Computer Graphics Laboratory provides the necessary computational expertise and resources required for this project.